吉林大学学报(医学版) ›› 2024, Vol. 50 ›› Issue (4): 963-969.doi: 10.13481/j.1671-587X.20240410

• 基础研究 • 上一篇    下一篇

鹿茸多肽对大鼠绝经后骨质疏松的改善作用及其机制

迟雪婷1,陈芳园1,皮子凤1,律广富2,王雨辰1,李银清1,黄晓巍1,3(),林喆1()   

  1. 1.长春中医药大学药学院临床药学与中药药理教研室,吉林 长春 130117
    2.长春中医药大学吉林省人参科学研究院中药药理组,吉林 长春 130117
    3.长春中医药大学东北亚中医药研究院 基础研究所,吉林 长春 130117
  • 收稿日期:2023-10-09 出版日期:2024-07-28 发布日期:2024-08-01
  • 通讯作者: 黄晓巍,林喆 E-mail:15948000740@163.com;linzhe1228@163.com
  • 作者简介:迟雪婷(1999-),女,吉林省松原市人,在读硕士研究生,主要从事心血管和内分泌药理学方面的研究。
  • 基金资助:
    吉林省科技厅科技发展计划项目(20210101200JC);吉林省发改委创新能力建设项目(2021C011);国家级大学生创新创业项目(202210199049)

Improvement effect of velvet antler polypeptide on postmenopausal osteoporosis in rats and its mechanism

Xueting CHI1,Fangyuan CHEN1,Zifeng PI1,Guangfu LYU2,Yuchen WANG1,Yinqing LI1,Xiaowei HUANG1,3(),Zhe LIN1()   

  1. 1.Department of Clinical Pharmacy and Chinese Medicine Pharmacology,School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China
    2.Department of Pharmacology of Traditional Chinese Medicine,Jilin Ginseng Academy,Changchun University of Chinese Medicine,Changchun 130117,China
    3.Basic Research Institute,Northeast Asia Institute of Chinese Medicine,Changchun University of Chinese Medicine,Changchun 130117,China
  • Received:2023-10-09 Online:2024-07-28 Published:2024-08-01
  • Contact: Xiaowei HUANG,Zhe LIN E-mail:15948000740@163.com;linzhe1228@163.com

摘要:

目的 探讨鹿茸多肽(VAP)对绝经后骨质疏松症(PMOP)模型大鼠的保护作用,并阐明其可能的作用机制。 方法 60只12周龄SD雌性大鼠随机分为假手术组、模型组、阿仑膦酸钠组(1 mg·kg-1·d-1阿仑膦酸钠灌胃)、低剂量VAP组(100 mg·kg-1·d-1VAP灌胃)、中剂量VAP组(200 mg·kg-1·d-1 VAP灌胃)和高剂量VAP组(300 mg·kg-1·d-1 VAP灌胃),每组10只。除假手术组外,其余各组大鼠摘除双侧卵巢,复制PMOP大鼠模型。双能X射线骨密度仪检测各组大鼠股骨骨密度(BMD),酶联免疫吸附试验(ELISA)法检测各组大鼠血清中血钙(Ca2+)、血磷(P)、骨碱性磷酸酶(BALP)和Ⅰ型前胶原N端前肽(PINP)水平,采用相关试剂盒检测各组大鼠血清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平,HE染色法观察各组大鼠骨组织病理形态表现,Western blotting法检测各组大鼠骨组织中磷脂酰肌醇-3激酶(PI3K)、磷酸化PI3K(p-PI3K)、蛋白激酶B(AKT)和磷酸化AKT(p-AKT)蛋白表达水平。 结果 与假手术组比较,模型组大鼠股骨BMD降低(P<0.01);与模型组比较,阿仑膦酸钠组、中剂量VAP组和高剂量VAP组大鼠股骨BMD升高(P<0.05或P<0.01)。与假手术组比较,模型组大鼠血清中Ca2+、P、BALP及PINP水平和SOD活性降低(P<0.05或P<0.01),MDA水平升高(P<0.01);与模型组比较,中剂量VAP组大鼠血清中P水平升高(P<0.01),阿仑膦酸钠组和高剂量VAP组大鼠血清中Ca2+、P、BALP及PINP水平和SOD活性升高(P<0.05或P<0.01),MDA水平降低(P<0.05)。HE染色,与假手术组比较,模型组大鼠骨组织中骨小梁纤细,大片断裂,髓腔扩大;与模型组比较,阿仑膦酸钠组、中剂量VAP组和高剂量VAP组大鼠骨组织中骨小梁粗壮,排列紧密,骨细胞数量多。Western blotting法,与假手术组比较,模型组大鼠骨组织中p-PI3K/PI3K和p-AKT/AKT比值降低(P<0.01);与模型组比较,各剂量VAP组大鼠骨组织中p-PI3K/PI3K比值升高(P<0.05或P<0.01),阿仑膦酸钠组和高剂量VAP组大鼠骨组织中p-AKT/AKT比值升高(P<0.01)。 结论 VAP对大鼠PMOP具有改善作用,其机制可能与VAP调控骨组织中PI3K/AKT信号通路及降低骨组织氧化应激有关。

关键词: 骨质疏松症, 鹿茸多肽, 氧化应激, 磷脂酰肌醇-3激酶/蛋白激酶B信号通路

Abstract:

Objective To discuss the protective effect of velvet antler peptide (VAP) on the postmenopausal osteoporosis (PMOP) model rats,and to clarify its possible mechanism. Methods A total of 60 twelve-week-old female SD rats were randomly divided into sham operation group, model group, alendronate sodium group (1 mg·kg?1·d?1 alendronate sodium administered via gavage), low dose of VAP group (100 mg·kg?1·d?1 VAP administered via gavage), medium dose of VAP group (200 mg·kg?1·d?1 VAP administered via gavage), and high dose of VAP group (300 mg·kg?1·d?1 VAP administered via gavage), and there were 10 rats in each group. Except for the sham operation group, the rats in the other groups underwent bilateral ovariectomy to establish the PMOP rat models. Dual-energy X-ray absorptiometry was used to detect the femur bone mineral density (BMD) of the rats in various groups;enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum calcium (Ca2+), serum phosphorus (P), bone alkaline phosphatase (BALP), and procollagen type Ⅰ N-terminal propeptide (PINP) of the rats in various groups; Kits were used to detect the activities of superoxide dismutase (SOD) and the levels of malondialdehyde (MDA) of the rats in various groups; HE staining was used to observe the pathomorphology of bone tissue of the rats in various groups; Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (AKT), and phosphorylated AKT (p-AKT) proteins in bone tissue of the rats in various groups. Results Compared with sham operation group, the BMD in femur of the rats in model group was decreased (P<0.01); compared with model group, the BMD in femur of the rats in alendronate sodium group, medium dose of VAP group, and high dose of VAP group was increased (P<0.05 or P<0.01). Compared with sham operation group,the levels of Ca2?, P, BALP, PINP, and SOD activity in serum of the rats in model group were decreased (P<0.05 or P<0.01), and the MDA level was increased (P<0.01); compared with model group, the level of P in serum of the rats in medium dose of VAP group was increased (P<0.01), and the levels of Ca2?, P, BALP, PINP and the activities of SOD in serum of the rats in alendronate sodium group and high dose of VAP group were increased (P<0.05 or P<0.01), and the level of MDA in serum was decreased (P<0.05). The HE staining results showed that compared with sham operation group, the bone trabeculae in bone tissue of the rats in model group were thin and fractured, and the medullary cavity was enlarged; compared with model group, the bone trabeculae in bone tissue of the rats in alendronate sodium group, medium dose of VAP group, and high dose of VAP group were thick and tightly arranged, and had more osteocytes. The Western blotting results showed that compared with sham operation group, the ratios of p-PI3K/PI3K and p-AKT/AKT in bone tissue of the rats in model group were decreased (P<0.01); compared with model group, the ratios of p-PI3K/PI3K in bone tissue of rats in different doses of VAP groups were increased (P<0.05 or P<0.01), and the ratios of p-AKT/AKT of the rats in alendronate sodium group and high dose of VAP group was increased (P<0.01). Conclusion VAP can improve PMOP in the rats, and its mechanisms may be related to the regulation of the PI3K/AKT signaling pathway and the reduction of oxidative stress in bone tissue by VAP.

Key words: Osteoporosis, Velvet antler polypeptides, Oxidative stress, Phosphatidylinositol-3 kinase/protein kinase B signaling pathway

中图分类号: 

  • R285.5